Zhu Changyu, Tong Rongsheng, Jiang Xiaolei, Xiao Hua, Guan Jianmei, Shu Jianchen
Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Genet. 2022 Feb 21;12:767834. doi: 10.3389/fgene.2021.767834. eCollection 2021.
Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is involved in the deacetylation of p53 in regulating cell cycle and is associated with cancers at the molecular level. In this study, we evaluated the prognostic value in hepatocellular carcinoma (HCC) based on data from The Cancer Genome Atlas (TCGA) database. Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between DNTTIP1 expression and clinicopathological features. Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors. Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to DNTTIP1. The correlations between DNTTIP1 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis (ssGSEA). DNTTIP1 was found to be upregulated with amplification in tumor tissues in multiple HCC cohorts. High DNTTIP1 expression was associated with poorer overall survival (OS) and disease-free survival (DFS). GSEA suggested that DNTTIP1 regulates the cell cycle mitotic, G1/S, and G2/M phases and Fc fragment of IgE receptor I (FCERI)-mediated NF-κB and MAPK pathway and Fc fragment of IgG receptor (FCGR) activation pathways. Notably, ssGSEA indicated that DNTTIP1 expression was positively correlated with infiltrating levels of Th2 cells, Tfh, NK CD56 bright cells, aDCs, T helper cells, Th1 cells, and macrophages. These findings suggest that DNTTIP1 is correlated with prognosis and immune infiltration in HCC, which lays a foundation for further study of the immune-regulatory role of DNTTIP1 in HCC.
脱氧核苷酸转移酶末端相互作用蛋白1(DNTTIP1)参与p53的去乙酰化以调节细胞周期,并且在分子水平上与癌症相关。在本研究中,我们基于来自癌症基因组图谱(TCGA)数据库的数据评估了其在肝细胞癌(HCC)中的预后价值。采用Kruskal-Wallis检验、Wilcoxon符号秩检验和逻辑回归来评估DNTTIP1表达与临床病理特征之间的关系。采用Cox回归和Kaplan-Meier方法评估预后相关因素。进行基因集富集分析(GSEA)以确定与DNTTIP1相关的关键通路。通过单样本基因集富集分析(ssGSEA)研究DNTTIP1与癌症免疫浸润之间的相关性。发现在多个HCC队列中,肿瘤组织中的DNTTIP1随着扩增而上调。高DNTTIP1表达与较差的总生存期(OS)和无病生存期(DFS)相关。GSEA表明DNTTIP1调节细胞周期的有丝分裂期、G1/S期和G2/M期以及IgE受体I(FCERI)介导的NF-κB和MAPK通路以及IgG受体(FCGR)激活通路的Fc片段。值得注意的是,ssGSEA表明DNTTIP1表达与Th2细胞、滤泡辅助性T细胞(Tfh)、自然杀伤CD56bright细胞、浆细胞样树突状细胞(aDCs)、辅助性T细胞、Th1细胞和巨噬细胞的浸润水平呈正相关。这些发现表明DNTTIP1与HCC的预后和免疫浸润相关,这为进一步研究DNTTIP1在HCC中的免疫调节作用奠定了基础。